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《Drug metabolism and pharmacokinetics》2019,34(5):308-316
LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel 18O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H218O in the presence of the enzyme, generating singly- and doubly-18O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery. 相似文献
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何慧 《中国继续医学教育》2020,(4):160-162
目的总结并归纳护理干预对急性心肌梗死患者负性情绪的影响。方法本文挑选100例医院急性心肌梗死患者(2017年2月—2018年2月)为对象。按建档时间分组,对照组50例患者(常规护理),分析组50例患者(加用人文性护理)。比较两组对疾病的了解程度及护理前后焦虑、抑郁等负性情绪的评分,随访1年,比较两组复发率。结果护理后分析组对疾病了解程度高于对照组(P<0.05);护理前分析组焦虑、抑郁评分同对照组无显著差异(P>0.05),提示可比;护理后,分析组焦虑、抑郁评分低于对照组(P<0.05);护理后分析组1年内复发率(8.00%)低于对照组(24.00%)(P<0.05)。结论在急性心肌梗死患者的护理中,人文性护理干预可显著改善患者负性情绪,改善患者预后,且可有效降低患者复发率。 相似文献
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Ludwig Labler Marius Keel Otmar Trentz Michael Heinzelmann 《European spine journal》2006,15(9):1388-1396
The use of vacuum assisted closure (V.A.C.) therapy in postoperative infections after dorsal spinal surgery was studied retrospectively. Successful treatment was defined as a stable healed wound that showed no signs of acute or chronic infection. The treatment of the infected back wounds consisted of repeated debridement, irrigation and open wound treatment with temporary closure by V.A.C. The instrumentation was exchanged or removed if necessary. Fifteen patients with deep subfascial infections after posterior spinal surgery were treated. The implants were exchanged in seven cases, removed completely in five cases and left without changing in one case. In two cases spinal surgery consisted of laminectomy without instrumentation. In two cases only the wound defects were closed by muscle flap, the remaining ones were closed by delayed suturing. Antibiotic treatment was necessary in all cases. Follow up was possible in 14 patients. One patient showed a new infection after treatment. The study illustrates the usefulness of V.A.C. therapy as a new alternative management for wound conditioning of complex back wounds after deep subfascial infection. 相似文献
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928株革兰阴性杆菌耐药性监测 总被引:27,自引:4,他引:23
目的:了解青岛地区临床分离的重要革兰阴性杆菌的耐药情况以指导合理用药。方法:2001年青岛3家医院临床分离的5种革兰阴性杆菌用Kirby-Bauer法进行药敏试验。结果:5种病原菌均占3家医院革兰阴性杆菌分离率的前5位,大肠埃希菌对氟喹诺酮类药物的耐药率达60%-87%,细菌对亚胺培南均呈高度敏感,但铜绿假单胞菌耐亚胺培南株占25.8%,头孢他啶的抗菌活性是三代头孢菌素中最高的;复方酶抑制剂表现出良好的抗菌活性。结论:细菌耐药问题仍是目前临床的严重问题,地域性的耐药性监测是必要的。 相似文献
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HBeAg阳性与阴性慢性乙型肝炎患者中医辨证及其相关指标的比较 总被引:2,自引:0,他引:2
目的探讨HBeAg阳性与阴性慢性乙型肝炎(慢乙肝)患者中医辨证及其相关指标的相关性。方法对226例慢乙肝患者进行中医辨证分型,检测乙肝两对半、乙肝病毒DNA定量和肝功能、肝纤维化指标。结果各证型的乙型肝炎病毒(HBV)水平呈一定规律性,肝郁脾虚型>肝肾阴虚型>湿热中阻型>脾肾阳虚型>瘀血阻络型,随着病情的活动、病程的推延,HBV水平逐渐下降。无论HBeAg阳性与阴性,慢乙肝患者肝郁脾虚、肝肾阴虚、脾肾阳虚、瘀血阻络各型与湿热中阻型相比肝功能和肝纤维化指标均存在显著性差异。结论各证型的HBV水平呈一定规律性,提示病毒滴度与中医病因病机的转化有一定关系。湿热中阻和瘀血阻络是肝纤维化的关键。 相似文献
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我们用麻醉的正常血压大鼠,大鼠的自体灌液后肢分别研究了美哌隆的降压作用强度、部位、维持时间和对心率的影响。实验结果提示:美哌隆降低动脉血压的作用除依赖于它对外周α_1受体的选择性阻滞外,还依赖于它对外周阻力血管的直接扩张作用。美哌隆在降压的同时也减慢心率,其降压作用和负性频率作用与剂量有关。 相似文献
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H. -J. Möller H. M. van Praag B. Aufdembrinke P. Bailey T. R. E. Barnes J. Beck H. Bentsen F. X. Eich L. Farrow W. W. Fleischhacker J. Gerlach K. Grafford B. Hentschel A. Hertkorn S. Heylen Y. Lecrubier J. P. Leonard P. McKenna W. Maier V. Pedersen A. Rappard W. Rein J. Ryan M. Sloth Nielsen R. -D. Stieglitz G. Wegener J. Wilson 《Psychopharmacology》1994,115(1-2):221-228
There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally. 相似文献